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Course: Opportunistic Fungi in the Immunocompromised Patient
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Therapeutic Approaches to Fungal Disease
 
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Therapeutic Approaches to Fungal Disease


Fungi are eukaryotic organisms that differ from bacteria and other prokaryotic organisms in many ways. Like other human cells, fungal cells contain a nucleus, endoplasmic reticulum, mitochondria, and other organelles. Most fungal cells possess a rigid cell wall, the basic units of which are high-molecular-weight polysaccharides such as chitin and glucan, which differ from the sugar moieties of bacterial cell walls. The plasma membrane acts as a barrier between the intra- and extracellular components. It is involved in cell-wall synthesis and is responsible for the selective transport of molecules. The most significant difference between human and fungal cell membranes is in the sterols present. Ergosterol, instead of cholesterol, is the primary component of the cell membrane in fungi [65]. The primary function of ergosterols is to modulate membrane fluidity and provide a "sparking" function used to initiate growth and increase the size of the yeast cell [65].

Development of successful antifungal agents has proved far more difficult than the development of antibacterial drugs. This is due in part to the eukaryotic fungal cell structure [66] coupled with the fact that since fungal infection tends to be subacute, duration of therapy has to be extended, thus exacerbating the challenge of nontoxic therapy. Billions of dollars have been invested in an enormous effort to develop new and improved antifungals. The primary agents currently licensed in the United States by the Food and Drug Administration (FDA) belong to 3 principal classes: the polyenes, the azoles, and the pyrimidines. In addition, a number of new agents are under investigation clinically, and still more are at the developmental stage. These agents act by interfering with either the cellular membrane, the smooth endoplasmic reticulum, or the cell nucleus. The latest experimental agents, the echinocandins and pneumocandins, target the fungal cell wall — a cell structure that human cells do not share (Fig 10).

figure 10






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Therapeutic Approaches to Fungal
   Amphotericin B
   Lipid Formulations of Amphotericin B
   Azole Antifungal Agents
   New Azoles Undergoing Clinical Trials
   Flucytosine
   Echinocandin/Pneumocandin Agents

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Course Number: V035B.043001

This CME Expires on July 1, 2003; no tests will be accepted after this date.

This course is accredited by The University of Pittsburgh School of Medicine, Center for Continuing Education




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